Tal Structure on the Tetrameric Fibrinogen-like Recognition Domain of Fibrinogen C Domain Containing 1 (FIBCD1) Protein*Received for publication, September 19, 2013, and in revised kind, November 27, 2013 Published, JBC Papers in Press, November 28, 2013, DOI 10.1074/jbc.M113.Annette K. Shrive1,two, Jesper B. Moeller?, Ian Burns, Jenny M. Paterson, Amy J. Shaw, Anders Schlosser? Grith L. Sorensen? Trevor J. Greenhough, and Uffe Holmskov?In the Analysis Institute of Science and Technologies in Medicine, College of Life Sciences, Keele University, Staffordshire ST5 5BG, United kingdom and also the �Department of Cardiovascular and Renal Study, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, DenmarkBackground: FIBCD1 is actually a tetrameric plasma membrane protein that uses a fibrinogen-like recognition domain (FReD) for pattern recognition of acetyl groups on chitin. Results: The x-ray structure of the FIBCD1 FReD reveals how FIBCD1 binds acetylated and sulfated molecules. Conclusion: FReD domains combine versatility with conservation to recognize their targets. Significance: The structure suggests how FIBCD1 binds acetylated pathogen-associated molecular patterns (PAMPS) and endogenous glycosaminoglycans. The higher resolution crystal structures of a recombinant fragment with the C-terminal fibrinogen-like recognition domain of FIBCD1, a vertebrate receptor that binds chitin, have been determined. The general tetrameric structure shows similarity in structure and aggregation for the horseshoe crab innate immune protein tachylectin 5A. The high affinity ligand N-acetylmannosamine (ManNAc) binds within the S1 website, predominantly by way of the acetyl group with the oxygen and acetamide nitrogen hydrogenbonded for the protein plus the methyl group inserted into a hydrophobic pocket. The binding of the ManNAc pyranose ring differs markedly in between the two independent subunits, but in all structures the binding in the N-acetyl group is conserved. In the native structure, a crystal contact benefits in among the independent protomers binding the first GlcNAc of your Asn340 N-linked glycan around the other independent protomer. Inside the ligand-bound structure this GlcNAc is replaced by the larger affinity ligand ManNAc. Moreover, a sulfate ion has been modeled into the electron density at a location similar to the S3 binding web-site in L-ficolin, whereas in the native structure an acetate ion has been placed within the S1 N-acetyl binding website, and also a sulfate ion has been placed adjacent to this web site.725728-43-8 Purity These ion binding web sites are ideally placed to receive the N-acetyl and sulfate groups of sulfated GalNAc residues of glycosaminoglycans which include chondroitin and dermatan sulfate.94928-86-6 Data Sheet Together, these structures give insight into important determinants of ligand selectivity, demonstrating versatility in recognition and binding even though sustaining conservation in N-acetyl and calcium binding.PMID:23255394 * This perform was supported by the Healthcare Analysis Council (to A. K. S., T. J. G.,and I. B.), Central Laboratory from the Investigation Councils (CLRC) Daresbury Laboratory, the Diamond Light Supply (Midlands BAG MX310), the Danish Health-related Analysis Council (to U. H.), the NOVO Nordic Foundation (to U. H.), the Lundbeck Foundation (U. H.), and Fonden til L evidenskabens Fremme (to U. H.). Author’s Choice–Final version full access. The atomic coordinates and structure variables (codes 4M7H and 4M7F) have already been deposited in the Protein Data Bank (http://wwpdb.org/). 1 Each authors contributed e.